Automated Insulin Delivery Versus Daily Injections for Hospital Diabetes Care

Official title

Inpatient Diabetes Management With Automated Insulin Delivery Systems Compared to Multiple Daily Injections With a Basal-bolus Regimen - a Randomized Controlled Trial

Overview

Aim The investigators aim to investigate if automated insulin delivery systems (AID) improve in-hospital glycemic and clinical outcomes in patients with type 2 diabetes compared to standard-of-care with a pen-basal-bolus insulin regimen manually titrated by general staff at Herlev-Gentofte Hospital and a clinical decision support system (GlucoTab) titrating the basal-bolus regimen automatically daily at Graz University Hospital. Population Hospitalized patients with type 2 diabetes in non-intensive care units (non-ICU) at medical wards at Copenhagen University Hospitals of Herley-Gentofte (affiliated with Steno Diabetes Center Copenhagen) and Medical University Hospital of Graz (N = 92). Design This is an investigator-initiated, two-armed, two-site, prospective, randomized, open-label, blinded endpoint (PROBE) trial. Objectives The objective is to determine the glycemic and clinical effects of inpatient AID systems in non-ICU patients with type 2 diabetes. Participants will be randomized in a usual-of-care and an AID arm. Diabetes management will be performed by usual care in the control arm based on a basal-bolus insulin regimen and point-of-care (POC) glucose testing. A continuous glucose monitoring (CGM) system (Abbott FreeStyle Libre 3) will be used in all groups for outcome analysis and comparison between the groups. The CGM will be blinded for the control arm, to not interfere with the usual of care because of the higher amount of glucose data. The AID-arm will be managed by an AID system with real-time CGM data transmitted to nursing stations. Outcomes Primary outcome: The primary outcome is the difference in CGM-recorded time in range (TIR) (70-180 mg/dl (3.9-10.0 mmol/l)) between the POC- and the CGM-arm according to the 2023 in-hospital CGM consensus during the entire hospital stay. Secondary outcomes: Outcomes are reported according to the 2023 in-hospital CGM consensus and specified in the protocol during the entire hospital stay, including three levels of time above range (TAR) 180-250mg/dl (10.0-13.9 mmol/l), \>250mg/dl (\>13.9 mmol/l), and \>180mg/dl (\>10.0 mmol/l); three levels of time below range (TBR) 54-70mg/dl (3.0-3.9 mmol/l), \<54mg/dl (\<3.0 mmol/l), and \<70mg/dl (\<3.9 mmol/l); events of hypoglycemia in three levels, 54-68mg/dl (3.0-3.8 mmol/l), \<54mg/dl (\< 3.0 mmol/l), and \<70mg/dl (\<3.9 mmol/l), where the glucose values between the two hypoglycemic events must all be \>70mg/dl (\>3.9 mmol/l) for at least 15 consecutive minutes(1), including prolonged hypoglycemic events (\> 120 minutes), recurrent hypoglycemic events (events preceded by another hypoglycemic event), and recurrent hypoglycemic days (percentage of days with at least one hypoglycemic event on separate days that is preceded by another in-hospital day with hypoglycemia(1)); mean glucose level; standard deviation (SD) of the CGM glucose distribution; coefficient of variation (CV); and insulin doses during hospitalization. Clinical outcomes: The investigator assess the length of hospital stay as calculated from time of admission until discharge; in-hospital mortality; admissions to intensive care unit; any in-hospital-related complications occurring at least one day after randomization and until discharge, as documented and defined by the treating physician in the electronic health record (e.g., acute kidney injurie, sepsis, etc.) Method For the usual-of-care-arm, glucose assessment is done by standard POC glucose testing and insulin is manually titrated by general staff at Herlev-Gentofte Hospital and the glucose assessment is done by standard POC glucose testing and insulin is manually titrated by the GlucoTab system titrating the basal-bolus regimen automatically daily at Graz University Hospital. For the AID-arm, CGM data informs in real time the mylife Ypsopump for automated insulin delivery. Device The investigational device is the AID system, containing of the mylife YpsoPump and the FreeStyle Libre 3 sensor.

Interventions

• Device automated insulin delivery system
  To date, no randomized controlled trials have evaluated inpatient use - including bolus insulin - in patients with infectious disease.
• Procedure GlucoTab
  Participants at Graz University Hospital are basal-bolus insulin regimen , however, insulin is not manually titrated, but titration is based daily on the GlucoTab system, a clinical decision support validated for the inpatient setting in titrating insulin for patients with type 2 diabetes as this is the usual of care at MUG. The GlucoTab-arm will be titrated initially by the principal Investigator or sub principal investigator and afterwards by the general ward nurses of MUG.
• Procedure Control-arm
  In the control-arm, glucose levels are assessed with POC glucose testing at 03:00 h, pre-prandial at breakfast, lunch, and dinner, and before bedtime (22:00 h) or for participants not eating at 03:00 h, 08:00 h, 12:00 h, 17:00 h, and 22:00 h. Those collected glucose levels will be automatically transferred to the EHR. If POC glucose testing is not prescribed or performed five times daily as standard of care, the research staff may encourage usual ward nurses to do so. The investigat will also mo

Primary outcome measures

• Time in range [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]

Secondary outcome measures (12)

• Time above range level 1 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Time above range level 2 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Time below range level 1 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Time below range level 2 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Hypoglycemic events level 1 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Hypoglycemic event level 2 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Recurrent hypoglycemic event [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Time at High Risk for Hypoglycemia [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Glycemia risk index [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Prolonged hypoglycemic events level 1 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Prolonged hypoglycemic event level 2 [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]
• Severe hypoglycemia [Time frame: From inclusion in the trial until discharge from hospital (up to 30 days)]

Eligibility criteria

Inclusion criteria

• A documented history of Type 2 diabetes mellitus (T2DM) which requires subcutaneous insulin therapy
• acute infectious disease of any kind
• age ≥ 18 years old
• willingness and ability to comply with theclinical investigation plan
• ability to communicate with the trial personal
• an expected length of hospital stay for at least 2 days after enrolment

Exclusion criteria

• Patients already using AID for their glycemic management
• Patients in use of an insulin pump
• Skin pathologies that hinder application of a FreeStyle Libre-3 CGM and mylife YpsoPump
• Participation in another trial, which could influence the outcome of the trial
• Any mental condition rendering the patient incapable of giving informed consent
• Known or suspected allergy to adhesive material/tape of the Libre-3-sensor and/or YpsoPump
• Any disease or condition which the investigator or treating physician feels would interfere with the trial or the safety of the patient
• Diagnoses/treatments/clinical parameters prohibiting use of Insulin/AID such as

• Estimated glomerular filtration rate (eGFR) <15 mL/min/1.73 m2 OR
• Treated with hydroxyurea/hydroxycarbamide OR
• Nutritional therapy (continuous enteral or parenteral feeding) OR
• Clinically relevant pancreatic disease OR
• Aystemic glucocorticoid treatment with prednisone equivalent dose >5 mg/day OR
• Expected to require admission to the intensive-care unit OR > Patients in dialysis

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Treatment

Study locations

Austria · 1 center

• University Hospital of Graz — Graz

Denmark · 1 center

• Steno Diabetes Center Copenhagen — Copenhagen

Publications

• Bally L, Thabit H, Hartnell S, Andereggen E, Ruan Y, Wilinska ME, Evans ML, Wertli MM, Coll AP, Stettler C, Hovorka R. Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care. N Engl J Med. 2018 Aug 9;379(6):547-556. doi: 10.1056/NEJMoa1805233. Epub 2018 Jun 25. PMID 29940126
• Olsen MT, Klarskov CK, Jensen SH, Rasmussen LM, Lindegaard B, Andersen JA, Gottlieb H, Lunding S, Pedersen-Bjergaard U, Hansen KB, Kristensen PL. In-Hospital Diabetes Management by a Diabetes Team and Insulin Titration Algorithms Based on Continuous Glucose Monitoring or Point-of-Care Glucose Testing in Patients With Type 2 Diabetes (DIATEC): A Randomized Controlled Trial. Diabetes Care. 2025 Apr PMID 39887698
• Sampson MJ, Singh H, Dhatariya KK, Jones C, Walden E, Bradley C. Psychometric validation and use of a novel diabetes in-patient treatment satisfaction questionnaire. Diabet Med. 2009 Jul;26(7):729-35. doi: 10.1111/j.1464-5491.2009.02754.x. PMID 19573123
• Benfield T, Jensen JS, Nordestgaard BG. Influence of diabetes and hyperglycaemia on infectious disease hospitalisation and outcome. Diabetologia. 2007 Mar;50(3):549-54. doi: 10.1007/s00125-006-0570-3. Epub 2006 Dec 23. PMID 17187246
• Shah BR, Hux JE. Quantifying the risk of infectious diseases for people with diabetes. Diabetes Care. 2003 Feb;26(2):510-3. doi: 10.2337/diacare.26.2.510. PMID 12547890
• Bertoni AG, Saydah S, Brancati FL. Diabetes and the risk of infection-related mortality in the U.S. Diabetes Care. 2001 Jun;24(6):1044-9. doi: 10.2337/diacare.24.6.1044. PMID 11375368
• YPU_eIFU_REF_700009439_BE-de_V01.pdf [Internet]. [cited 2024 Nov 23]. Available from: https://www.mylife-diabetescare.com/files/media/03_Documents/01_YpsoPump/IFU/1.5/YPU_eIFU_REF_700009439_BE-de_V01.pdf
• Rubin R, Khanna NR, McIver LA. Aspart Insulin. 2024 Jun 8. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-. Available from http://www.ncbi.nlm.nih.gov/books/NBK500030/ PMID 29763206

Identifiers

NCT: NCT07645079 · Inpatient-AID

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗